In vivo body composition measurements are vital to research in growth and development, the aging process, the malnutritions, and pathologies such as osteoporosis and the acquired immunodeficiency syndrome. In vivo neutron activation analysis (IVNA) has become the most basic, the most precise, and the most accurate reference standard for quantifying human body composition, though rarely available. Its effectiveness has been demonstrated in studies on osteoporosis, cancer, effects of growth hormone, thalassemia, nutritional deficiencies, and alcoholism. However, its application is limited in the range of subject height and weight for which calibrations are available. This proposal defines 1) the optimal use of IVNA to study body composition in four clinical projects which require precise and accurate measurements in human subjects; 2) the use of Monte Carlo simulations and phantom studies to improve the precision and the accuracy of the IVNA studies and to extend them to leaner and fatter subjects; 3) the application of new compartmental models to analyze the data; and 4) the development of the BNL IVNA facility to a reference laboratory for IVNA techniques and applications; and 5) the establishment of translation tables to calibrate proposed non-invasive methods which may serve as surrogates for IVNA. This project will assemble in one administrative structure the mechanism for applying the state-of-the-art techniques for measuring elemental and compartmental body composition methods to clinical projects: IVNA to measure total body C, N, Na, P, Cl, K, and Ca, which provide also total body fat and lean mass; dual photon absorptiometry to measure bone mineral content and body lean and fat mass; isotopic dilution; total body electrical conductivity; and bioelectric impedance analysis. The basic science for calibration, validation, and analytic modeling will be centered in the Core laboratory at BNL, with participation by the Columbia University group. The clinical projects will be centered int eh laboratories of the four principal investigators of the projects in New York City, Nassau County, and Boston, with the administrative core centered at the St. Luke's site in New York. Results from these research projects together will provide a wide range of normal reference data, and a significant reduction in cost for the planned studies in each project. This proposal will strengthen the field of body composition research by establishing national standard for most body composition measurement techniques.